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2010 Fiscal Year Final Research Report

Molecular Analyses of Osteoblastic Niche and its Application with the Development of Nano Science

Research Project

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Project/Area Number 18109011
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NODA Masaki  Tokyo Medical and Dental University, 難治疾患研究所, 教授 (50231725)

Co-Investigator(Kenkyū-buntansha) EZURA Yoichi  東京医科歯科大学, 難治疾患研究所, 准教授 (50333456)
HAYATA Tadayoshi  東京医科歯科大学, 難治疾患研究所, 助教 (40420252)
Project Period (FY) 2006 – 2010
Keywords骨 / 軟骨代謝学
Research Abstract

To understand the mechanism of boneformation factors that are involved in the regulation and pathology, we have been examining molecular bases with respect to the micro environment. We identified that and CIZ is involved in the regulations ob bone information by altering the signaling of osteoblasts. CIZ and ECM proteins are regulating cell attachment and transcription. BMP is a most critical cytokine for bone information and implicated in niche regulation. Niche for bone cells and the regulation of cells in such location has not been well elucidated. As interaction of local and systemic hormone is important for coordinate regulation of bone formation we focused on parathyroid hormone (PTH). Such systemic hormonal control exerts its effect through the regulation of local target tissues, which in turn regulate upstream signals in a feedback loop. Parathyroid hormone receptor (PPR) transgenic mice expressing a constitutively active form of the receptor (caPPR) specifically in cells of th … More e osteoblast lineage have a high bone mass phenotype. In these mice, OPN deficiency further increased bone mass. Bone formation was also found to be controlled by ANA and Cnot7 that inhibit BMP. Epigentic link and PTH dependent regulation by M-CSF and MCP is also found to be important. Regeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low-dose bone morphogenetic protein 2 (BMP-2). Combination treatment with EP4A and low-dose BMP-2 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low-dose BMP-2-induced cell differentiation and activation of transcription events in osteoblasts. These data indicate that combined delivery of EP4A and low-dose BMP-2 via nanogel-based hydrogel provides a new system for bone repair. Less

  • Research Products

    (56 results)

All 2011 2010 2009 2008 2007 2006 2005 Other

All Journal Article (37 results) (of which Peer Reviewed: 37 results) Presentation (15 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Per-1 is a specific clock gene regulated by parathyroid hormone (PTH) signaling in osteoblasts and is functional for the transcriptional events induced by PTH2011

    • Author(s)
      Hanyu R, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 112

      Pages: 433-438

    • Peer Reviewed
  • [Journal Article] Nanogel-based scaffold delivery of prostaglandin E(2) receptor-specific agonist in combination with a low dose of growth factor heals critical-size bone defects in mice2011

    • Author(s)
      Kamolratanakul P, Noda M, et al.
    • Journal Title

      Arthritis Rheum 63(4)

      Pages: 1021-1033

    • Peer Reviewed
  • [Journal Article] Schnurri-2 deficiency counteracts against bone loss induced by ovariectomy2010

    • Author(s)
      Nagao M, Noda M, et al.
    • Journal Title

      Journal of Cellular Physiology 226

      Pages: 573-578

    • Peer Reviewed
  • [Journal Article] Cbl-b Enhances Runx2 Protein Stability and Augments Osteocalcin Promoter Activity in Osteoblastic Cell Lines2010

    • Author(s)
      Ampornaramveth Salingcarnboriboon on oriboon Noda M, et al.
    • Journal Title

      Journal of Cellular Physiology 224

      Pages: 743-747

    • Peer Reviewed
  • [Journal Article] Nemo-like kinase (NLK) expression in osteoblastic cells and suppression of osteoblastic differentiation2010

    • Author(s)
      Nifuji A, Noda M, et al.
    • Journal Title

      Experimental Cell Research 316

      Pages: 1127-1136

    • Peer Reviewed
  • [Journal Article] Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption2010

    • Author(s)
      Mizoguchi F, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 109

      Pages: 866-875

    • Peer Reviewed
  • [Journal Article] Combinatory effects of androgen receptor deficiency and hind limb unloading on bone2009

    • Author(s)
      Saita Y, Noda M, et al.
    • Journal Title

      Hormone and Metabolic Research 41

      Pages: 822-828

    • Peer Reviewed
  • [Journal Article] ANA deficiency enhances BMP-induced ectopic bone formation via transcriptional events2009

    • Author(s)
      Miyai K, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 284

      Pages: 10593-10600

    • Peer Reviewed
  • [Journal Article] Methylation status of CpG-islands in the promoter regions of signature genes during chondrogenesis of human synovium-derived 5 mesenchymal stem cells2009

    • Author(s)
      Ezura Y, Noda M, et al.
    • Journal Title

      Arthritis & Rheumatism 60

      Pages: 1416-1626

    • Peer Reviewed
  • [Journal Article] Angiotensin II type 2 receptor blockade increases bone mass2009

    • Author(s)
      Izu Y, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 284

      Pages: 4857-4864

    • Peer Reviewed
  • [Journal Article] Osteoblastic Bone Formation Is Induced by Using Nanogel-Crosslinking Hydrogel as Novel Scaffold for Bone Growth Factor2009

    • Author(s)
      Hayashi C, Noda M, et al.
    • Journal Title

      Journal of Cellular Physiology 220

      Pages: 1-7

    • Peer Reviewed
  • [Journal Article] Osteopontin Negatively Regulates parathyroid hormone receptor signaling in osteoblasts2008

    • Author(s)
      Ono N, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 283

      Pages: 19400-19409

    • Peer Reviewed
  • [Journal Article] OPN deficiency suppresses appearance of odontoclastic cells and resorption of the tooth root induced by experimental force application2008

    • Author(s)
      Chung CJ, Noda M, et al.
    • Journal Title

      Journal of Cellular Physiology 214

      Pages: 614-620

    • Peer Reviewed
  • [Journal Article] A new Trem family member, Treml4, binds to dead cells and is a DAP12 linked marker for subsets of mouse macrophages and dendritic cells2008

    • Author(s)
      Hemmi H, Noda M, et al.
    • Journal Title

      Journal of Immunology 182

      Pages: 1278-1286

    • Peer Reviewed
  • [Journal Article] Expression and tyrosine phosphorylation of Crk associated substrate lymphocyte type (Cas-L) protein in human neutrophils2008

    • Author(s)
      Nakamoto T, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 105

      Pages: 121-128

    • Peer Reviewed
  • [Journal Article] Ciz, a transcription factor with a nucleocytoplasmic shuttling activity, interacts with C-propeptides of type I collagen2008

    • Author(s)
      Hayata T, Noda M, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 368

      Pages: 205-210

    • Peer Reviewed
  • [Journal Article] Transient Receptor Potential Vanilloid 4 Deficiency Suppresses Unloading-Induced Bone Loss2008

    • Author(s)
      Mizoguchi F, Noda M, et al.
    • Journal Title

      Journal of Cellular Physiology 216

      Pages: 47-53

    • Peer Reviewed
  • [Journal Article] JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion2008

    • Author(s)
      Kawamata A, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 103

      Pages: 1037-1045

    • Peer Reviewed
  • [Journal Article] Constitutively active parathyroid hormone receptor signaling in cells in osteoblastic lineage suppresses mechanical unloading-induced bone resorption2007

    • Author(s)
      Ono N, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 25509-25516

    • Peer Reviewed
  • [Journal Article] Lack of schnurri-2 expression associates with reduced bone remodeling and osteopenia2007

    • Author(s)
      Saita Y, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 12907-12915

    • Peer Reviewed
  • [Journal Article] NF-kB p50 and p52 regulate RANKL and TNF-induced osteoclast precursor differentiation by activating c-Fos and NFATc12007

    • Author(s)
      Yamashita T, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 282

      Pages: 18245-18253

    • Peer Reviewed
  • [Journal Article] PlexinD1 deficiency induces defects in axial skeletal morphogenesis2007

    • Author(s)
      Kanda T, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 101

      Pages: 1329-1337

    • Peer Reviewed
  • [Journal Article] Nanogel-based delivery system enhances PGE(2) effects on bone formation2007

    • Author(s)
      Kato N, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 101

      Pages: 1063-1070

    • Peer Reviewed
  • [Journal Article] Ihh/Gli2 Signaling Promotes Osteoblast Differentiation by Regulating Runx2 Expression and Function2007

    • Author(s)
      Shimoyama A, Noda M, et al.
    • Journal Title

      Molecular Biology of the Cell 18

      Pages: 2411-2418

    • Peer Reviewed
  • [Journal Article] Cnot7 Null Mice Exhibit High Bone Mass Phenotype and Modulation of BMP Actions2007

    • Author(s)
      Washio-Oikawa K, Noda M, et al.
    • Journal Title

      Journal of Bone Mineral Research 22

      Pages: 1217-1223

    • Peer Reviewed
  • [Journal Article] Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration2007

    • Author(s)
      Hayashi C, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 101

      Pages: 979-986

    • Peer Reviewed
  • [Journal Article] Osteopontin deficiency enhances anabolic action of EP4 agonist at a sub-optimal dose in bone2007

    • Author(s)
      Kato N, Noda M, et al.
    • Journal Title

      Journal of Endocrinology 193

      Pages: 171-182

    • Peer Reviewed
  • [Journal Article] Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo2007

    • Author(s)
      Hino K, Noda M, et al.
    • Journal Title

      Bone 40

      Pages: 852-860

    • Peer Reviewed
  • [Journal Article] A crucial role for matrix metalloproteinase 2 in osteocytic canalicular formation and bone metabolism2006

    • Author(s)
      Inoue K, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 281

      Pages: 33814-88824

    • Peer Reviewed
  • [Journal Article] Runx2 is a Target of Mechanical Unloading to Alter Osteoblastic Activity and Bone Formation in Vivo2006

    • Author(s)
      Salingcarnboriboon R, Noda M, et al.
    • Journal Title

      Endocrinology 147

      Pages: 2296-2305

    • Peer Reviewed
  • [Journal Article] Osteopontin deficiency suppresses high phosphate load-inhate load-induced bone loss via specific modulation of osteoclasts2006

    • Author(s)
      Koyama Y, Noda M, et al.
    • Journal Title

      Endocrinology 147

      Pages: 3040-3049

    • Peer Reviewed
  • [Journal Article] Expression Analysis of LacZ gene placed in the locus of Cnot7 exhibits its activity in osteoblasts in vivo and in mineralized nodules in vitro2006

    • Author(s)
      Washio-Oikawa K, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 99

      Pages: 538-544

    • Peer Reviewed
  • [Journal Article] Osteopontin is associated with nuclear factor kB gene expression during tail-suspension-induced bone loss2006

    • Author(s)
      Ishijima M, Noda M, et al.
    • Journal Title

      Experimental Cell Research 312

      Pages: 3075-8083

    • Peer Reviewed
  • [Journal Article] Unloading-induced bone loss was suppressed in gold-thioglucose treated mice2006

    • Author(s)
      Hino K, Noda M, et al.
    • Journal Title

      Journal of Cellular Biochemistry 99

      Pages: 845-852

    • Peer Reviewed
  • [Journal Article] Sympathetic regulation of osteoclastogenesis is required for gonadectomy-induced bone loss and antagonized by CART2005

    • Author(s)
      Elefteriou F, Noda M, et al.
    • Journal Title

      Nature 433

      Pages: 7028

    • Peer Reviewed
  • [Journal Article] CIZ reduces adult bone mass in vivo via inhibition of BMP-induced bone formation2005

    • Author(s)
      Morinobu M, Noda M, et al.
    • Journal Title

      Journal of Experimental Medicine 201

      Pages: 961-970

    • Peer Reviewed
  • [Journal Article] Unloading induces osteoblastic cell suppression and osteoclastic cell activation to lead to bone loss via sympathetic nervous system2005

    • Author(s)
      Kondo H, Noda M, et al.
    • Journal Title

      Journal of Biological Chemistry 280

      Pages: 30192-30200

    • Peer Reviewed
  • [Presentation] Anabolic action ofPTH signaling on bone activated expression of a clock gene, Per-12011

    • Author(s)
      Ryo Hanyu, Masaki Noda, et al.
    • Organizer
      第1回国際スポートロジー学会学術集会
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2011-03-05
  • [Presentation] Ovariectomy induced bone loss was prevented by the deficiency of jund which determines osteoblastic activity and basal levels of bone mass2010

    • Author(s)
      Kawamata A, Noda M, et al.
    • Organizer
      The 9th Asian Congress on Oral and Maxillofacial Surgery
    • Place of Presentation
      Kuala Lumpur, Malaysia
    • Year and Date
      20101125-20101128
  • [Presentation] Schnurri2 Deficiency Increases all of 1,25(OH)2D3,Renal 25-hydroxyvitamin D 1-α Hdroxylase, PTH, FGF23、Serum Calcium and 6 Phosphate in Association with Hypercalcificationin in Joints2010

    • Author(s)
      Nagao M, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Osteopontin Plays a Pivotal Role Sympathetic Control of Bone Mass2010

    • Author(s)
      Nagao M, Noda M, et al
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Unloading-induced Suppression of B-lymphogenesis and Expansion of Peripheral Monocyte/macrophage Lineage Cells is Preserved in the Mice Deficient for Osteopontin2010

    • Author(s)
      Ezura Y, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Adregergic Receptor Regulates Anabolic Action of Constitutively Active Form of PTH/PTHrP Receptor Signaling2010

    • Author(s)
      Hanyu R, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Cnot3, a Novel Critical Regulator of a mRNA Stability, is Involved in the Maintenance of the Bone Mass and the Bone Structure in Senile Osteoprosis Model2010

    • Author(s)
      Watanabe C, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] PTH Anabolic Action is Influenced by the Deficiency of TRPV4 in Bone2010

    • Author(s)
      Kamolratanakul P, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto,Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Identification of Novel Molecule for Melanoma Malignancy- Role of CIZ2010

    • Author(s)
      Miyai K, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Dullard, a Novel BMP Inhibitor, Targets Smad1 to Suppress BMP-dependent Transcription in Mammalian Osteoblastic Cells2010

    • Author(s)
      Hayata T, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Deficiency of Dok-1 and Dok-2, Ras-Erk Pathway Inhibitors, Enhances Bone Loss in Postmenopausal Osteoprosis Model of Mice2010

    • Author(s)
      Miyajima D, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Nck1, a Molecular Adaptor Prerequisite for Cell Motility, is Stimulated by Bone Morphogenetic Protein and Contributes to Maintain Bone Mass2010

    • Author(s)
      Hanyu R, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] TRPV4(Transient Receptor Potential Vanilloid 4), a Mechanosensor for Bone Is Required for the Maintenance of Bone Mineral Density of Mandible Exposed to Occlusal Force.2010

    • Author(s)
      Suzuki T, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] CIZ Expression is Enhanced by Inflammatory Stimulation and Transcriptionally Regulates the RANKL Promoter2010

    • Author(s)
      Nakamoto T, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Presentation] Genetic Conversiion of Osteoclast Precursor to be Responsive to Light-controlled Cation Channel Activation Enhances Differentiation Upon Modulation of their Membrane Potential2010

    • Author(s)
      Notomi T, Noda M, et al.
    • Organizer
      The 32nd Annual Meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Toronoto, Ontario, Canada
    • Year and Date
      20101015-20101019
  • [Book] Mechanosensing Biology2011

    • Author(s)
      Masaki Noda
    • Total Pages
      219
    • Publisher
      Springer
  • [Remarks] ホームページ等

    • URL

      http://www.tmd.ac.jp/mri/section/advanced/mp/index.html

  • [Patent(Industrial Property Rights)] 骨形成促進物質とナノゲルを含有する骨形成用生体材料2007

    • Inventor(s)
      秋吉一成、野田政樹
    • Industrial Property Rights Holder
      秋吉一成、野田政樹
    • Industrial Property Number
      特許,特願2007-554906
    • Filing Date
      2007-07-17
  • [Patent(Industrial Property Rights)] 抗オステオポンチン抗体及びその用途/ANTI-OSTEOPONTIN AND USE THEREOF2006

    • Inventor(s)
      上出利光、今重之、佐伯行彦、横崎恭之、野田政樹、山本宣哉
    • Industrial Property Rights Holder
      上出利光、今重之、佐伯行彦、横崎恭之、野田政樹、山本宣哉
    • Industrial Property Number
      特許,特願2006-281027
    • Filing Date
      2006-10-16

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Published: 2012-01-26   Modified: 2016-04-21  

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